Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome.

BACKGROUND AND OBJECTIVES: MCT8 deficiency is a rare genetic leukoencephalopathy caused by a defect of thyroid hormone transport across cell membranes, particularly through blood brain barrier and into neural cells. It is characterized by a complex neurological presentation, signs of peripheral thyrotoxicosis and cerebral hypothyroidism. Movement disorders (MDs) have been frequently mentioned in this condition, but not systematically studied. METHODS: Each patient recruited was video-recorded during a routine outpatient visit according to a predefined protocol. The presence and the type of MDs were evaluated. The type of MD was blindly scored by two child neurologists experts in inherited white matter diseases and in MD. Dystonia was scored according to Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). When more than one MD was present, the predominant one was scored. RESULTS: 27 patients were included through a multicenter collaboration. In many cases we saw a combination of different MDs. Hypokinesia was present in 25/27 patients and was the predominant MD in 19. It was often associated with hypomimia and global hypotonia. Dystonia was observed in 25/27 patients, however, in a minority of cases (5) it was deemed the predominant MD. In eleven patients, exaggerated startle reactions and/or other paroxysmal non-epileptic events were observed. CONCLUSION: MDs are frequent clinical features of MCT8 deficiency, possibly related to the important role of thyroid hormones in brain development and functioning of normal dopaminergic circuits of the basal ganglia. Dystonia is common, but usually mild to moderate in severity, while hypokinesia was the predominant MD in the majority of patients.

Ruxolitinib in Aicardi-Goutières syndrome.

Aicardi-Goutières Syndrome (AGS) is a monogenic leukodystrophy with pediatric onset, clinically characterized by a variable degree of neurologic impairment. It belongs to a group of condition called type I interferonopathies that are characterized by abnormal overproduction of interferon alpha, an inflammatory cytokine which action is mediated by the activation of two of the four human Janus Kinases. Thanks to an ever-increasing knowledge of the molecular basis and pathogenetic mechanisms of the disease, Janus Kinase inhibitors (JAKIs) have been proposed as a treatment option for selected interferonopathies. Here we reported the 24 months follow-up of the fifth AGS patient treated with ruxolitinib described so far in literature. The treatment was globally well tolerated; clinical examinations and radiological images demonstrated a progressively improving course. It is however to note that patients presenting with mild and spontaneously improving course have been reported. Large natural history studies on AGS spectrum are strongly required in order to get a better understanding of the results emerging from ongoing therapeutic trials on such rare disease.

Comparison between an Ascenda and a silicone catheter in intrathecal baclofen therapy in pediatric patients: analysis of complications.

OBJECTIVE In this single-center study the authors investigated the complications occurring before and after the introduction of the new Ascenda intrathecal catheter (Medtronic Inc.) in pediatric patients treated with intrathecal baclofen therapy (ITB) for spasticity and/or dystonia. METHODS This was a retrospective review of 508 children who had received ITB, 416 with silicone catheters in the 13 years between September 1998 and September 2011 and 92 with Ascenda catheters in the 3 years between September 2011 and August 2014. The authors evaluated major complications such as infections, CSF leaks treated, and problems related to the catheter or pump, and they compared the 2 groups of patients who had received either a silicone catheter or an Ascenda catheter implant. RESULTS One hundred twenty patients in the silicone group (29%) and 1 patient in the Ascenda group (1.1%; p < 0.001) had a major complication. In the silicone group 23 patients (5.5%) were affected by CSF leakage and 75 patients (18%) experienced 82 catheter-related events, such as occlusion, dislodgment, disconnection, or breakage, which required catheter replacement. In the Ascenda group, only 1 patient (1.1%) was affected by CSF leakage. CONCLUSIONS To the authors' knowledge, this study is the first in the literature to compare the performance of the new Ascenda catheter, introduced in 2011, with the traditional silicone catheter for intrathecal drug infusion. In their analysis, the authors found that the Ascenda catheter can reduce major complications related to the catheter after ITB pump implantation. Further investigation is necessary to expand on and confirm their results.

Analysis of complications in 430 consecutive pediatric patients treated with intrathecal baclofen therapy: 14-year experience.

OBJECT: This single-center study investigated adverse events that occurred in children and adolescent patients treated with intrathecal baclofen (ITB) therapy for spasticity and/or dystonia. METHODS: In a 14-year period, 430 consecutive patients with a mean age of 13.3 ± 5.9 years received ITB over a mean follow-up period of 8.6 ± 3.8 years (range 12 months to 14 years). Eighty-nine percent of these patients had cerebral palsy. Major complications, defined as those that required a surgical intervention, were infections, CSF leaks, and device problems related to the catheter or pump. Assessing infections, the authors compared the 2 groups of patients implanted with an ITB system by either the subcutaneous or subfascial technique. The temporal distribution of events related to the catheter was also considered. RESULTS: At least 1 complication was present in 25% of the patients: 9.3% experienced an infection, 4.9% a CSF leak, 15.1% a problem with the catheter, and 1% a problem related to the pump. Five percent of the assessed patients suffered more than 1 complication. The rate of infections was significantly lower (p < 0.001) in patients with the pump placed subfascially compared with those with the pump placed subcutaneously. A higher rate of infection was found after pump replacement compared with the first pump implantation (10.6% vs 6%, respectively). Catheter problems were the most common complication and occurred more frequently during the 1st year after the implant. CONCLUSIONS: While ITB is an effective treatment to manage spasticity of different origins, adverse events may occur and need to be managed. The surgical procedure should be meticulous and different techniques may have a diverse impact on the infection rate, which is the most critical complication. Despite the adverse events that occurred in this study, the majority of patients were satisfied with the treatment received.

Intrathecal baclofen and motor function in cerebral palsy.

AIM: The aim of this retrospective analysis was to determine the impact of intrathecal baclofen (ITB) therapy on motor function in patients with cerebral palsy (CP). METHOD: We studied 37 patients (18 males, 19 females) with CP treated with ITB (mean age at implant 13 y 7 mo, SD 7 y). Eighteen patients were affected by spastic diplegia, 12 by spastic quadriplegia, six by dystonic quadriplegia, and one by hemidystonia. Nine participants were in Gross Motor Function Classification System (GMFCS) level II, 13 in level III, seven in level IV, and eight in level V. Motor function was assessed by the Gross Motor Function Measure (GMFM) before the treatment and 12 months after the implant. RESULTS: The collected data showed an increase in the total median GMFM score in the overall population (p<0.001) and in every GMFM dimension (p<0.05) except for dimension D (standing). The analysis by degree of impairment revealed that patients with severe impairment and those with mild to moderate impairment improved the total median GMFM score (p<0.001 and p<0.05 respectively). Analysis by age showed that the best improvements in GMFM scores were reached by patients younger than 18 years old (p<0.05). Spasticity and dystonia, assessed by means of the Ashworth and Barry-Albright Dystonia scales, significantly decreased 12 months after the implant (p<0.001 and p<0.05 respectively). Finally, a subjective questionnaire administered to patients/caregivers revealed an overall improvement in participants' functional abilities. INTERPRETATION: The results suggest that ITB therapy is an effective treatment for managing spasticity and dystonia, and for improving motor function in children with CP.

Forced-use, without therapy, in children with hemiplegia: preliminary study of a new approach for the upper limb.

BACKGROUND: Forced use (FU) is an emerging treatment for children with hemiplegic cerebral palsy (CP). It involves constraining the unaffected arm and no additional treatment of the affected arm. Our study examined a new approach to FU in children with hemiplegic CP: that is, restraint of the unaffected limb and no rehabilitation. METHODS: Ten children with hemiplegic CP aged between 5 and 9 years were compared with 10 control children (aged between 5 and 8 y). All participants were classified as MACS level II.The FU group wore a fixed cast, on the unaffected arm for 21 consecutive days, and, such as the control group, did not receive any physical therapy.All participants were assessed by the Melbourne Assessment of Unilateral Upper Limb Function and the Shriners Hospital Upper Extremity Evaluation. RESULTS: A statistically significant increase in both the functional scales was already apparent after cast removal and was maintained during follow-ups. The total Melbourne Assessment of Unilateral Upper Limb Function percentage score increased significantly to 9.5% and 12.3% on 3-week and 3-month follow-up examinations, respectively (P<0.05). A statistically significant increase was observed in 2 of the 3 parts of the Shriners Hospital Upper Extremity Evaluation: spontaneous use (P<0.05) and the ability of the involved limb to grasp and release (G/R) (P<0.05). CONCLUSIONS: These preliminary results suggest that FU without rehabilitation improves the spontaneous use and function of the affected upper limb. In children with hemiplegia, this approach may be an economically viable means of upper limb treatment that has no side effects. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions to Authors for complete description of level of evidence.

Upper limbs function after intrathecal baclofen therapy in children with secondary dystonia.

BACKGROUND: Different studies show the efficacy of intrathecal baclofen therapy (ITB) in patients with secondary dystonia because of cerebral palsy. These studies only report improvements related to dystonia reduction; however, none of them have assessed whether such benefit is reflected in limb function. The purpose of our study is to determine whether the effects ITB therapy in patients with secondary dystonia to cerebral palsy, in addition to reducing dystonia, may also improve upper limb function. METHODS: Eleven patients with secondary dystonia, classified as levels 3 and 4 of the Gross Motor Function Classification System, were treated with ITB. The mean age at implant was 11.3 (SD+/-3.02) years.Before treatment and 12 months after implant, the patients were evaluated by the Melbourne Assessment of Unilateral Upper Limb and the Barry Albright scale to assess upper limb function and dystonia, respectively. RESULTS: We found a statistically significant improvement in both scales. The Melbourne scale total percentage score, for both limbs, increased in all patients (P<0.05). Dystonia assessed by the Barry Albright scale scale decreased significantly by 15% from baseline to 12 months follow-up (P<0.05). CONCLUSIONS: In patients with secondary dystonia treated with ITB, functional improvement of the upper limbs was observed in addition to dystonia reduction. In patients with secondary dystonia, ITB is a treatment that aims to achieve a general reduction of dystonia; this study want to show the influence that this reduction has to functional ability of patient. LEVEL OF EVIDENCE: Therapeutic study: level 4.

Effect of intrathecal baclofen on dystonia in children with cerebral palsy and the use of functional scales.

BACKGROUND: The literature available shows that spasticity in patients with cerebral palsy (CP) is reduced by intrathecal baclofen (ITB) treatment, and various studies suggest that this treatment can also be used in dystonic patients. The aim of the present study was to evaluate dystonia treated with ITB in children with CP. METHODS: Data of 19 patients affected by dystonia as an outcome of infant CP in patients belonging to level V of Gross Motor Function Classification System treated with ITB were collected. The mean age at implant is 8.49 years.The patients are assessed using Barry-Albright Scale and Burke-Fahn-Marsden Scale before treatment and at 3, 6, and 12 months postimplant. RESULTS: The results showed a statistically significant improvement (P < 0.001) in the total scores of the 2 scales after just 3 months of treatment, an improvement that was maintained for the 1-year period of follow-up. The results also revealed a reduction in dystonias, an improvement in posture, and an easing of the task of the caregivers in managing the patient as a result of treatment with ITB. CONCLUSIONS: In patients belonging to level V of Gross Motor Function Classification System and treated with ITB, a decrease in frequency and severity of dystonia is observed. This improvement eases caregiver in patient management. LEVEL OF EVIDENCE: Therapeutic Level IV.

Upper limb function after intrathecal baclofen treatment in children with cerebral palsy.

BACKGROUND: The literature shows that intrathecal baclofen (ITB) treatment in patients with cerebral palsy (CP) is able to reduce spasticity. The purpose of this work is to evaluate the motor function of the upper limbs in patients with CP treated with ITB. METHODS: A consecutive series of 20 patients with spastic CP (mean age at implant, 11.4 years) implanted with pumps in our center was studied. These patients were classified using the Gross Motor Function Classification System. The patients were followed up over a 12-month period for assessment of the upper limb function with the Melbourne Assessment of Unilateral Upper Limb Function scale. RESULTS: The data show a reduction of upper limb spasticity in all 20 patients (P < 0.05). The Melbourne scale shows a statistically significant improvement of the total score (P < 0.05) and an improvement of the subskills of range of movement, target accuracy, and fluency. Twenty-five percent of patients showed a clinically significant improvement. CONCLUSION: The subjects with CP of different degrees of severity had an improvement in the quality of the upper limb function and showed overall satisfaction with the results achieved. The study also shows the importance of evaluating the quality of upper limb function in children with CP treated with ITB therapy.